Incidence Rates Of Thromboembolic Events Research Articles

Incidence and risk factors for thromboembolic events in pediatric-onset inflammatory bowel disease: A French population-based study

IntroductionPatients with inflammatory bowel disease (IBD) are at higher risk of thromboembolic events (TE). In pediatric-onset IBD, more data on incidence and risk factors of venous (VTE) and arterial events (ATE) at the population level are needed to guide thromboprophylaxis. MethodsAll patients aged ≤ 16 years diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 1988 and 2011 in the prospective EPIMAD population-based registry were followed until 2013. Every TE occurring during the follow-up period was included. ResultsA total of 1,344 patients were included: 1,007 with CD and 337 with UC, and a median diagnosis age of 14.3 years. After a median follow-up of 8.3 years, 2 (0.15 %) ATE and 15 (1.1 %) VTE occurred at median age of 20.4 years. The global incidence rate of thromboembolic events was 1.32 per 1000 person-years. Periods of active disease (HR=8.4, p = 0.0002), the 3-month-period following surgery (HR=16.4, p = 0.0002) and hospitalization (HR=21.7, p < 0.0001) were found to be associated with an increased risk of VTE. A lower rate of VTE was found in patients treated with 5-aminosalicylates (HR=0.1, p = 0.002). ConclusionThe risk of TE was low in this population. VTE were strongly associated with active disease, surgery and hospitalization.

Romiplostim for chemotherapy induced thrombocytopenia in solid tumors: A meta-analysis.

e24137 Background: Chemotherapy-induced thrombocytopenia (CIT), defined as platelets &lt; 100,000/mcL persisting for ≥3-4 weeks post-chemotherapy affects 20-25% of cases necessitating platelet transfusions or dose reductions leading to treatment delays and impacting patient outcomes. (1,2) Despite multiple studied agents, there are no established guidelines. Romiplostim, a thrombopoietin receptor agonist approved for immune thrombocytopenic purpura, stands out. NCCN suggests its use, but pooled analyses are lacking. Our meta-analysis addresses this gap, exploring romiplostim's efficacy in CIT management. Methods: We performed a systematic search of PUBMED, EMBASE, and COCHRANE databases for studies that evaluate the use of romiplostim in the setting of CIT for solid tumors. The primary endpoint was the proportion of patients that showed improvement in platelet counts in response to romiplostim. Secondary endpoints were the proportion of patients that continued full dose chemotherapy dose on romiplostim and incidence of thromboembolic events. Pooled proportions were calculated along with 95% confidence intervals (CI) using a random-effects model. I2 statistic was used to depict inter-study heterogeneity. Results: A total of 10 single arm studies - 3 prospective studies, 3 case series, and 4 retrospective studies were included. The pooled outcomes were: significant improvement of platelet count above 100K with response to romiplostim therapy in 80.53% patients [95 % CI 72.47 - 87.48, I2 = 69%], proportion of patients that continued full dose chemotherapy on romiplostim was 70.89% [95% CI 63.40 - 77.84, I2 = 0%], and incidence of thromboembolic events was 6.81% [ 95% CI 3.64 – 10.89, I2 = 35%]. Variables like platelet transfusions, bleeding events, type and stage of cancer were not reported uniformly and hence subgroup analyses could not be performed. Conclusions: Our analysis reveals that romiplostim improved the platelet counts in majority of patients with underlying CIT associated with solid tumors. It also shows that a majority of the patients were able to resume their full dose chemotherapy when maintained on romiplostim. The incidence rate of thromboembolic events with romiplostim believed to be consistent with what expected of this population with majority having advanced/high-risk malignancies. Given its efficacy, romiplostim may be used for routinely managing CIT in solid tumors. This analysis is limited by lack of comparative studies and warrant further randomized trials to confirm the safety and efficacy of romiplostim in this patient population.

Risk Factors for Thromboembolic and Bleeding Events in Patients After the Fontan Operation (Insights from the National Database of Health Insurance Claims of Japan)

Risk stratification of thromboembolic events (TEs) and bleeding events is important for the appropriate selection of thromboprophylaxis in patients after the Fontan operation. Therefore, we clarified the risk factors for TEs and bleeding events in patients after the Fontan operation using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. We conducted a retrospective cohort study including 2,515 patients who underwent the Fontan operation between June 2011 and September 2019. The end points were TEs and bleeding events within 1year of the Fontan operation analysis. We analyzed the risk factors for these end points using a multivariate analysis. In total, 1,903 patients were included in the analysis. The median age at the time of the Fontan operation was 3 (1 to 22) years, and 1,067 patients (56%) were male. The incidence rates of TEs and bleeding events were 12% and 11%, respectively. Age (odds ratio [OR] 1.1 per 1 year older, p <0.05) was an independent risk factor for TEs. Thromboprophylaxis with aspirin after the Fontan operation significantly reduced TEs (OR 0.3, p <0.05). A history of postoperative hemorrhage (OR 1.5, p <0.05) and the use of a potassium channel blocker (OR 2.1, p <0.05) were independent risk factors for bleeding events. In conclusion, aspirin was found to reduce the risk of TEs within 1 year of the Fontan operation. The results of this study will be useful in selecting effective and safe thromboprophylaxis in patients after the Fontan operation.

The relationship between fasting blood glucose level and thromboembolism events in patients with non-valvular atrial fibrillation

Objective: To explore the relationship between fasting blood glucose level and thromboembolism events in patients with non-valvular atrial fibrillation (NVAF). Methods: This was an observational study based on data from a multicenter, prospective Chinese atrial fibrillation registry cohort, which included 18 703 consecutive patients with atrial fibrillation (AF) in 31 hospitals in Beijing from August 2011 to December 2018. Patients were divided into 5 groups according to status of comorbid diabetes and fasting glucose levels at admission: normal blood glucose (normal glucose group), pre-diabetes group, strict glycemic control group, average glycemic control group and poor glycemic control group. Patients were followed up by telephone or outpatient service every 6 months. The primary follow-up endpoint was thromboembolic events, including ischemic stroke and systemic embolism. The secondary endpoint was the composite endpoint of cardiovascular death and thromboembolic events. Kaplan-Meier survival analysis and multifactorial Cox regression were used to analyze the correlation between fasting glucose levels and endpoint events. Results: The age of 18 703 patients with NVAF was (63.8±12.0) years, and there were 11 503 (61.5%) male patients. There were 11 877 patients (63.5%) in normal blood glucose group, 2 023 patients (10.8%)in pre-diabetes group, 1 131 patients (6.0%) in strict glycemic control group, 811 patients in average glycemic control group and 2 861 patients(4.3%) in poor glycemic control group. Of the 4 803 diabetic patients, 1 131 patients (23.5%) achieved strict glycemic control, of whom 328 (29.0%) were hypoglycemic (fasting blood glucose level<4.4 mmol/L at admission). During a mean follow-up of (51±23) months (up to 82 months), thromboembolic events were reported in 984 patients (5.3%). The survival curve analysis of Kaplan Meier showed that the incidence rates of thromboembolic events in normal glucose group, pre-diabetes group, strict glycemic control group, average glycemic control group and poor glycemic control group were 1.10/100, 1.41/100, 2.09/100, 1.46/100 and 1.71/100 person-years, respectively (χ²=53.0, log-rank P<0.001). The incidence rates of composite endpoint events were 1.86/100, 2.17/100, 4.08/100, 2.58/100, 3.16/100 person-years (χ²=72.3, log-rank P<0.001). The incidence of thromboembolic events and composite endpoint events in the other four groups were higher than that in the normal blood glucose group (P<0.001). Multivariate Cox regression analysis showed that compared with normal glucose group, the risk of thromboembolism increased in pre-diabetes group(HR=1.23, 95%CI 1.00-1.51, P=0.049), strict glycemic control group(HR=1.32, 95%CI 1.06-1.65, P=0.013) and poor glycemic control group(HR=1.26, 95%CI 1.01-1.58, P=0.044). Conclusion: Both high or low fasting glucose may be an independent risk factor for thromboembolic events in patients with NVAF.

SP7.1.2 DVT and Abdominoplasty: A Holistic 8-point protocol-based approach to prevent DVT

Abstract Aim Plastic surgery as a speciality is afflicted with one of the highest incidence rates of thromboembolic events, with abdominoplasty procedures known to assimilate the greatest rates of Deep Vein Thrombosis (DVT). Methods A total of 1078 abdominoplasty patients were enrolled onto an 8-point prophylaxis protocol with an inclusive holistic approach over a 7- year period. A 4-week smoking, HRT and COC cessation period was imposed on all patients and a maximum BMI score of 40 was required of all preoperative patients. Participants were administered with compression stockings, flowtrons and enoxaparin. Individuals with a DVT history were also required to be 1-year treatment free prior to surgery. Furthermore, the protocol necessitated post-operative deambulation of fit patients within 4 hours. Results Between 2008 and 2013, no incidence of DVT was recorded in all 1078 abdominoplasty surgery patients, indicating the potential for this protocol to lead to a significantly lower incidence than any previously published methodology. Due to the zero-incidence rate of DVT, different hypotheses of DVT proportions were tested to find out the rates that could be statistically consistent with our sample, thereby providing conservative incidence rate estimates. Conclusion This 8-point DVT prophylaxis protocol is the first non-criteria based inclusive protocol aimed at preventing abdominoplasty-associated DVT. As a result, not a single incident of DVT was recorded over the seven-year period of this study. We therefore believe that a holistic and procedure-specific approach to prophylaxis can drastically reduce the occurrence of DVT in abdominoplasty surgery.

1058 DVT And Abdominoplasty: A Holistic 8-Point Protocol-Based Approach to Prevent DVT

Abstract Aim Plastic surgery as a speciality is afflicted with one of the highest incidence rates of thromboembolic events, with abdominoplasty procedures known to assimilate the greatest rates of Deep Vein Thrombosis (DVT). Method A total of 1078 abdominoplasty patients were enrolled onto an 8-point prophylaxis protocol with an inclusive holistic approach over a 7- year period. A 4-week smoking, HRT and COC cessation period was imposed on all patients and a maximum BMI score of 40 was required of all preoperative patients. Participants were administered with compression stockings, flowtrons and enoxaparin. Individuals with a DVT history were also required to be 1-year treatment free prior to surgery. Furthermore, the protocol necessitated post-operative deambulation of fit patients within 4 hours. Results Between 2008 and 2013, no incidence of DVT was recorded in all 1078 abdominoplasty surgery patients, indicating the potential for this protocol to lead to a significantly lower incidence than any previously published methodology. Due to the zero-incidence rate of DVT, different hypotheses of DVT proportions were tested to find out the rates that could be statistically consistent with our sample, thereby providing conservative incidence rate estimates. Conclusions This 8-point DVT prophylaxis protocol is the first non-criteria based inclusive protocol aimed at preventing abdominoplasty-associated DVT. As a result, not a single incident of DVT was recorded over the seven-year period of this study. We therefore believe that a holistic and procedure-specific approach to prophylaxis can drastically reduce the occurrence of DVT in abdominoplasty surgery

Incidence of Thrombo-Embolic Events in Relation to Activated Prothrombin Complex Concentrate Exposure: A Literature Meta-Analysis

IntroductionThe development of factor VIII (FVIII) inhibitory antibodies is one of the major challenges of the treatment of hemophilia, because it hinders FVIII replacement for the treatment and prevention of bleeding events (Leissinger 2015). Two products are currently available to control bleeding in patients with inhibitors: the activated prothrombin complex concentrate (aPCC; FVIII inhibitor bypassing activity, FEIBA VH; Shire plc, USA) and recombinant activated factor VII (rFVIIa; NovoSeven, Bagsvaerd, Denmark). Both agents have shown similar efficacy, with some patients responding better to one over the other (Astermark 2007). Both agents have been associated with the development of thromboembolic events (TEEs) (Aledort 2004). Aim of this study was to estimate TEE incidence in patients with congenital hemophilia with inhibitors and acquired hemophilia exposed to aPCC, by using a meta-analytic approach based on published scientific literature.MethodsA systematic review of the literature was carried out in Medline, according to PRISMA guidelines, from inception date to March 2017. The incidence rate of TEEs was estimated via a meta-analytic approach by using a Generalized Linear Mixed Model based on a Poisson distribution.Stratified analyses according to study design (prospective vs. retrospective), hemophilia type (congenital vs. acquired) and treatment modality (on-demand, prophylaxis and surgery) have been conducted.ResultsWe identified a total of 144 papers through the electronic literature search and out of the 61 fully evaluated articles, 39 studies with TEE data related to the use of aPCC in patients with congenital hemophilia with inhibitor or acquired hemophilia were included in the meta-analysis. The studies included were published from 1980 to 2016, providing information on safety related to 678,447 aPCC infusions (7,291 infusions as on-demand treatment, 77,203 in prophylaxis, 3,296 in surgery and 590,657 in unspecified treatment modalities).In the 39 studies included overall, 46 TEEs were reported: 13 disseminated intravascular coagulation (DIC), 11 ischemic coronary syndrome (ICS), 4 pulmonary embolism (PE), 3 thrombotic cerebrovascular accidents (CVA), 3 deep vein thrombosis (DVT), 3 superficial vein thrombosis (SVT), 6 unspecified thrombosis (unreported location) and 3 fibrinogen reduction. No thrombotic microangiopathic events have ever been reported. Out of the 39 studies included, 31 (79%) reported no TEEs.The estimated pooled TEE incidence rate was 2.87 (95% CI 0.32-25.40) per 100,000 aPCC infusions. When stratifying for retrospective and prospective studies, 35 TEEs in 649,343 aPCC infusions (pooled incidence rate, 5.42 per 100,000 infusions), and 11 TEEs in 29,104 infusions (pooled incidence rate, 1.09 per 100,000 infusions) were respectively reported. TEE incidence rate in patients treated with aPCC on-demand was 5.09 per 100,000 infusions, while in patients treated with prophylaxis, no TEEs were reported. Five TEEs were reported in 11 studies in hemophilia patients with inhibitors undergoing surgery, being the pooled TEE incidence rate 112.03 per 100,000 aPCC infusions. Finally, pooled TEEs incidence rate in acquired hemophilia patients was 287.79 per 100,000 infusions, but less than 0.01 per 100,000 infusions in congenital hemophilia patients.ConclusionsThe pooled incidence rate was lower than 3 TEEs per 100,000 aPCC infusions, demonstrating a relatively low risk and confirming previous figures reported (Erlich 2002, Aledort 2004). Stratified analysis showed that the incidence is even lower in patients with congenital hemophilia and no TEE in prophylaxis. These findings provide robust evidence of safety of aPCC over almost 40 years of published studies. DisclosuresRota:ASHLEY COMMUNICATIONS ON BEHALF OF SHIRE FOR SHIRE SYMPOSIUM PARTICIPATION AS A SPEAKER AT THE ISTH 2017 CONGRESS: Honoraria. Cortesi:Shire: Research Funding. Crea:Shire: Employment, Equity Ownership. Gringeri:Shire: Employment. Mantovani:Daiichi Sankyo: Consultancy; Shire: Research Funding; Bayer AG: Consultancy; Boehringer Ingelheim: Research Funding; Janssen-Cilag: Research Funding.

LONG-TERM RESULTS OF AORTIC VALVE REPLACEMENT

Valvular heart disease makes up about 25% of all heart diseases. Of all the valvular heart diseases, aortic valvular disease is reported as more common. According to data from surgical hospitals, isolated aortic stenosis occurs in 44-68% of cases of aortic defects. Among patients with aortic valvular disease of non-rheumatic genesis, mesenchymal dysplasia causes the defect in 20% of cases, and in Europe and the United States, up to 10% of the population suffers from this disease. Aortic defects lead to the occurrence and progression of heart failure, cardiac arrhythmias and, as a consequence, a decrease in the life quality and life expectancy. Heart valve replacement is the most effective method for correcting heart defects that enables to eliminate the substrate of pathological changes, improve intracardiac hemodynamics and the life quality of patients. The evolution of various models of artificial valves creates conditions for the choice of surgical approaches to the treatment of aortic defects and a decrease in postoperative mortality rates in patients in the remote. At the same time, there are no large-scale studies in the scientific space of our country devoted to investigating the long-term consequences of aortic valve replacement by modern valve prostheses. There are questions whether it is appropriate to perform on the Ross operation in adults that entails the necessity of constant reoperations on the pulmonary artery valve and progressive dysfunction of the transplanted pulmonary valve in the high pressure areas of the arterial circle.&#x0D; The aim of this study is to investigate the characteristics of aortic valve replacement and the quality of life of the operated patients in long-term period.&#x0D; The study group included 634 patients with isolated aortic failure, who were operated on at N.N. Amosov National Institute of Cardiovascular Surgery from January 1, 2005 to January 1, 2007. The average follow-up period was 11.3 ± 0.9 years. The main indicators studied for the 15-year period were as follows: survival rate, stability of good and satisfactory results, incidence of thromboembolic complications, and reoperations.&#x0D; The study has demonstrated the following results for 15 year period: survival rate is 57.4%, stability of good results is 35.3%, incidence rate of thromboembolic events is 79.7%, and reoperations were required in 95.4% of all cases. The maze procedure was performed on in 21 (6,9%) patients. Concomitant CABG was observed in 93 (5.0%) patients. Reoperations were performed in cases of risks for thrombosis (panus, paraprost. fistula) of aortic prostheses (n=5), endocardytis (n=3); A-V blockade (pacemaker) was performed in 11 (1.6%) patients&#x0D; Best results of aortic valve replacement were observed in remote period in patients with II-III NYHA class with presence of sinus rhythm. The patients, who are at high risk of cardiovascular events, must be under close followed-up. The level of thromboembolic complications did not differ in terms of the type of implanted prosthesis. Labyrinth surgery should be performed on to restore sinus rhythm, as well as to reduce the progress of heart failure and prevent thromboembolic complications.&#x0D; Aortic valve replacement with the maze operation enables to renew sinus rhythm at the hospital stage quite successfully.

Low Embolic Risk from Short Duration Atrial Fibrillation following Anatomic Lung Resection

Objectives&#x0D; There is no consensus regarding the merits of anticoagulation following short duration atrial arrhythmia and anatomic lung resection. We hypothesized that the risk of embolic event following episodes of atrial fibrillation (AF) lasting less than 48 hours is low and even with an elevated CHA2DS2-VASC score should not incur the risk of long-term full dose anticoagulation contrary to recommendations.&#x0D; Design &amp; Intervention&#x0D; A retrospective review was performed of a prospectively maintained database of all patients undergoing anatomic lung resection at a single institution from 2014 to 2019. Patients who had new onset post-operative atrial fibrillation (POAF) were queried as to their co-morbidities, the length of arrhythmia, discharge with anticoagulation, and any post-operative embolic events.&#x0D; Main Outcome Measures&#x0D; There were 565 patients who underwent anatomic lung resection. 40 patients (7.1%) developed new POAF that lasted a median of one day. In 32 patients (80%), POAF lasted for less than 48 hours. There were 28 males and 12 females, median age of 73 years. These patients underwent segmentectomy (2/40), lobectomy (24/40) and pneumonectomy (14/40). Twenty-nine patients were discharged home without anticoagulation. Median follow-up was 22 month (range 1.3 – 62.8 month). Two patients had embolic events and these two were discharged home without anticoagulation. The overall incidence rate of thromboembolic events was 3.2% per person year.&#x0D; Conclusions&#x0D; Our data suggest that the risk of arterial embolic events is low in patients with new, short duration atrial fibrillation post anatomical lung resection. Anticoagulation may not be necessary in these patients and can be given selectively.

P90.02 BRAF Mutation And Peridiagnosis Thromboembolic Events In Advanced NSCLC Patients

Metastatic lung cancer is associated with an increased risk of thromboembolic events (TEE). Certain molecular subtypes of lung cancer, as patients with tumors harboring ALK or ROS1 gene rearrangements, have been recently associated with higher risk of TEE, in the range of 20-30%. Whether BRAF mutant lung cancer is associated with higher risk of TEE is unknown. We aimed to describe the incidence, characteristics, and time of onset of TEE in advanced BRAF mutant non-small-cell lung cancer (NSCLC) patients. We performed a retrospective search of BRAF mutant advanced NSCLC patients (stage IIIB or greater) diagnosed in our institution between October 2016 and February 2020. BRAF status was assessed by NGS in tissue/plasma or both as part of molecular pre-screening for clinical trials (Oncomine Focus Assay®; FoundationOne®; Guardant360®). Clinicopathologic and molecular data were extracted from electronic medical records. BRAF mutations were annotated and divided into Class I (V600) and Class II/III/VUS (non-V600) using OncoKB database. Venous TEE (deep venous thrombosis [DVT], superficial venous thrombosis [SVT] or pulmonary embolism [PE]) and arterial TEE (myocardial infarction [MI], cerebrovascular accident [CVA], peripheral arterial disease [PAD] or mesenteric ischemia [MIS]), number of events and dates were annotated. BRAF mutation was identified in 11/192 patients (incidence 5.7%): BRAF V600E in 2 cases (1%), and non-V600 in 9 cases (4.7%). Adenocarcinoma was the histology for all the cases. The incidence rate of TEE was 36.4% (4/11 patients). A total of 9 TEE were documented among 4 patients, as 3 of them developed several events, both arterial and venous. The TEE were DVT (n=2), SVT (n=1), PE (n=2), CVA (n=3), MIS (n=1). TEE was the form of disease presentation in 3/4 cases (acute stroke in 2 cases). TEE were found in 1 patient with V600E mutation and in 3 with non-V600. TEE were found more frequently in patients with PS ≥1, low albumin and Khorana score ≥2. Type of treatment was not related to TEE: 1 patient BRAF V600E mutated was treated with dabrafenib + trametinib without TEE, 4 patients were treated with immune-checkpoint inhibitors (1 with TEE) and 2 cases of TEE were detected before the initiation of treatment. Median overall survival was shorter in patients with TEE vs. without-TEE: 2.3 months vs 29 months (p=0.047). BRAF mutant lung cancer could be associated with a higher risk of TEE, both arterial and venous, and worse survival. If these results are confirmed in larger cohorts, prophylactic anticoagulation may be recommended in these patients.

Deep Vein Thrombosis (DVT) and Abdominoplasty: A Holistic 8-Point Protocol-Based Approach to Prevent DVT.

Plastic surgery as a specialty is afflicted with one of the highest incidence rates of thromboembolic events, with abdominoplasty procedures known to assimilate the greatest rates of deep vein thrombosis (DVT). The aim of this study was to develop a prophylactic protocol to reduce the rate of DVT occurrence postabdominoplasty. Over a 7-year period 1078 abdominoplasty patients were enrolled onto a holistic 8-point prophylaxis protocol. For a 4-week period before the operation all patients were required to stop smoking, and to cease hormone replacement therapy and combined oral contraception. All patients were required to have a preoperative BMI of less than 40 kg/m2. Participants were supplied with compression stockings, external pumping devices, and enoxaparin. Individuals with a history of DVT were also required to be 1-year treatment free prior to surgery. Furthermore, the protocol required postoperative ambulation of fit patients within 4 hours. Between 2008 and 2013, no incidence of DVT was recorded in all 1078 abdominoplasty surgery patients, indicating the potential for this protocol to lead to a significantly lower incidence than any previously published methodology. Previous studies of DVT incidence were reviewd to identify rates statistically significantly similar to our sample, thereby providing conservative incidence rate estimates. This 8-point DVT prophylaxis protocol is the first noncriteria-based inclusive protocol aimed at preventing abdominoplasty-associated DVT. A holistic and procedure-specific approach to prophylaxis can drastically reduce the occurrence of DVT in abdominoplasty surgery.With over 116,000 procedures performed annually in the United States, abdominoplasty has become one of the most popular and sought-after surgeries in the plastic and cosmetic field.1 Despite its ever-increasing popularity and the advancement of techniques, abdominoplasty-as with any other surgery-has its complications, including infection, seroma, hematoma, thrombosis, embolism, scarring, and even death. Complication rates as high as 37% have been reported, with some studies reporting a 16% major complication rate.2 One of the most serious and troubling complications for both surgeon and patient is deep vein thrombosis (DVT). With over 1 million patients tested, an estimated 250,000 cases of DVT are diagnosed per year in the United States alone.

Interactions of Key Hematological Parameters with Red Cell Distribution Width (RDW) Are Associated with Incidence of Thromboembolic Events (TEs) in Polycythemia Vera (PV) Patients: A Machine Learning Study (PV-AIM)

Interactions of Key Hematological Parameters with Red Cell Distribution Width (RDW) Are Associated with Incidence of Thromboembolic Events (TEs) in Polycythemia Vera (PV) Patients: A Machine Learning Study (PV-AIM)

Clinical Performance of Nonvitamin K Antagonist Oral Anticoagulants in Real-World Obese Patients with Atrial Fibrillation.

The prevalence of both atrial fibrillation (AF) and obesity has steadily increased. Nonvitamin K antagonist oral anticoagulants (NOACs) have been shown to be more effective and safer than vitamin K antagonists (VKAs) for long-term stroke prevention in patients with nonvalvular AF. There are still limited data in the literature regarding performance of NOACs in obese patients with AF in the "real world." The aim of our study was to compare the safety and effectiveness of NOACs versus well-controlled VKA therapy in obese AF patients in a "real-world" setting. Here, we have considered patients with AF and obesity (body mass index [BMI] > 30 kg/m2) on NOAC or VKA therapy included in the multicenter Atrial Fibrillation Research Database (NCT03760874). The occurrence of major bleedings (MBs) and thromboembolic events (composite of ischemic stroke, transient ischemic attack, and systemic embolism) was respectively considered primary safety and effectiveness outcomes. We identified 1,047 AF patients with obesity who received NOAC (n = 272) or VKA (n = 775) treatment. After propensity score matching analysis, 248 NOAC and 496 VKA recipients with similar clinical characteristics, including BMI (34.8 ± 3.4 in NOAC vs. 35.1 ± 3.8 in the VKA group; p = 0.50), were evaluated. The mean follow-up was 39 ± 7 months. The incidence rate of thromboembolic events was 1.10 per 100 person-years (0.67 in NOAC vs. 1.28 in the VKA group; hazard ratio [HR]: 0.52; 95% confidence interval [CI]: 0.22-1.22; p = 0.19). The incidence rate of MB was 1.9 per 100 person-years (1.1 in NOAC vs. 2.28 in the VKA group; HR: 0.46; 95% CI: 0.24-0.88; p = 0.04). The incidence rate of intracranial hemorrhage was 0.4 per 100 person-years (0.27 in NOAC vs. 0.47 in the VKA group; HR: 0.57; 95% CI: 0.12-2.73; p = 0.48). A positive net clinical benefit (NCB) of NOACs over VKAs was found (+0.91). Presence of anemia (HR: 1.75; p = 0.003) and concomitant use of antiplatelet drugs (HR: 2.41; p = 0.001) were found to be independent predictors of MB; moreover, age (HR: 1.65; p = 0.003) was an independent predictor of thromboembolic events. Our data support the hypothesis of safe and effective use of NOACs in patients with AF and obesity, justified by a statistically significant lower incidence of MB and a favorable NCB over VKAs.

Atrial Fibrillation and Mitral Regurgitation: Clinical Performance of Direct Oral Anticoagulants in a Real-World Setting.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is frequently present in patients with mitral regurgitation (MR). Currently, there is a lack of real-world evidence specifically addressing the clinical performance of direct oral anticoagulants (DOACs) in patients with AF and concomitant MR. Therefore, the aim of the present study was to assess the efficacy and safety profile of DOACs therapy in patients with AF and MR. Data for this study were sourced from the Atrial Fibrillation Research Database in the Department of Cardiology at Monaldi Hospital. The database was queried for AF patients with MR who were prescribed DOACs therapy. The primary safety outcome was defined as the annual incidence rate of major bleeding events and the primary effectiveness outcome as the annual incidence rate of all events classified as ischemic stroke, transient ischemic attacks, and systemic embolisms. Consecutive AF patients with concomitant mild to severe MR who received DOACs therapy (n = 259) were included. Patients were dichotomized in 2 groups according to MR severity: a mild-to-moderate group (MR 1-2+; n = 151) and a moderate-to-severe group (MR 3-4+; n = 108). The incidence rate of major bleedings was significantly higher in MR 3-4+ group (3.92%) compared with the MR 1-2+ group (1.18%; hazard ratio [HR]: 3.2; 95% CI: 1.4-7.3; P = .0059). The incidence rate of thromboembolic events between MR 3-4+ group (0.66%) and MR 1-2+ group (0.62%) was not significantly different (HR: 0.75; P = .823). In the present study, there was no difference in the efficacy profile of DOACs between AF patients with mild-to-moderate and moderate-to-severe MR. Considering the increased bleeding risk, a close and careful follow-up should be warranted for patients with moderate-to-severe MR.

Clinical Outcome of Edoxaban vs. Vitamin K Antagonists in Patients with Atrial Fibrillation and Diabetes Mellitus: Results from a Multicenter, Propensity-Matched, Real-World Cohort Study.

Diabetes mellitus (DM) is a chronic metabolic disease which is independently associated with unfavorable clinical outcomes in patients with atrial fibrillation (AF). Few real-world data are available about the clinical performance of non-vitamin K oral anticoagulants (NOACs) among patients with atrial fibrillation and diabetes. The aim of our propensity score-matched cohort study was to compare the safety and effectiveness of Edoxaban versus well-controlled vitamin K antagonists (VKAs) therapy among this population. In this study, we considered patients with AF and diabetes on Edoxaban or VKAs therapy included in the multicenter Atrial Fibrillation Research Database (NCT03760874). The occurrence of major bleedings (MB) and thromboembolic events (a composite of ischemic stroke, transient ischemic attack, systemic embolism) was respectively considered primary safety and effectiveness outcome. We identified 557 AF patients with diabetes who received Edoxaban (n: 230) or VKAs (n: 327) treatment. After propensity score matching analysis, 135 Edoxaban and 135 VKA recipients with similar clinical characteristics were evaluated. The mean follow-up was 27 ± 3 months. The incidence rate of thromboembolic events (TE) was 3.0 per 100 person-years (1.11 in Edoxaban vs. 1.9 in the VKA group, hazard ratio (HR): 0.59; 95% confidence interval (CI), 0.14 to 2.52; p = 0.48). The incidence rate of major bleedings (MB) was 3.7 per 100 person-years (1.2 in Edoxaban vs. 2.7 in the VKA group, HR: 0.43; 95% CI: 0.10 to 1.40; p = 0.14). The incidence rate of intracranial hemorrhage was 0.35 per 100 person-years in Edoxaban vs. 0.74 in the VKA group (HR: 0.49; 95% CI: 0.05 to 5.54; p = 0.56). A positive net clinical benefit (NCB) of Edoxaban over VKAs was found (+1.39). Insulin therapy (HR: 1.76, p = 0.004) and glycated hemoglobin (HR: 1.17, p = 0.002) were found to be independent predictors of TE; moreover, the concomitant use of antiplatelet drugs (HR: 2.41, p = 0.001) was an independent predictor of MB. Conclusions: Our data support the hypothesis of the safety and efficacy of Edoxaban for use in patients with AF and diabetes, justified by a favorable NCB over VKAs.

Secondary stroke prophylaxis in atrial fibrillation patients with chronic kidney disease: a nationwide cohort study.

Oral anticoagulation (OAC) therapy as secondary stroke prophylaxis in atrial fibrillation (AF) patients with chronic kidney disease (CKD) remains unexplored and poses a clinical treatment dilemma. We assessed the long-term risk of thromboembolic events according to post-stroke OAC therapy in AF patients with CKD after their first ischaemic stroke. We identified Danish AF patients with CKD who presented with first-time ischaemic stroke from 2005 to 2014. Chronic kidney disease was defined as a diagnosis code for CKD before baseline, defined as 100 days after stroke discharge. Post-stroke antithrombotic therapy (OAC therapy and antiplatelet therapy) was identified from prescription claims from discharge to baseline. Cumulative incidences and adjusted hazard ratios (HRs) of thromboembolic events according to post-stroke OAC therapy were examined. Of 1252 AF patients with CKD presenting with ischaemic stroke, 631 (50.4%) patients were on OAC therapy and 621 (49.6%) were on antiplatelet therapy alone at baseline [median age 76 (interquartile range, IQR 71-83) and 80 (IQR 72-86), respectively]. The median follow-up period was 1.9 years (IQR 0.8-3.6). Cumulative incidence rates of thromboembolic events and bleeding showed no significant difference between those on OAC therapy and antiplatelet therapy. The results from the multivariable analysis revealed similar results: thromboembolic risk was not modified by OAC treatment [adjusted HR 0.89, 95% confidence interval (CI) 0.73-1.09] nor was the risk of bleeding (adjusted HR 0.88, 95% CI 0.67-1.17). Oral anticoagulation in patients with CKD and prior stroke was not associated with a reduced risk of recurrent thromboembolic events compared with antiplatelet therapy.

Thromboembolic Outcomes of Different Anticoagulation Strategies for Patients with Atrial Fibrillation in the Setting of Hypertrophic Cardiomyopathy: A Systematic Review.

Limited data is available assessing the efficacy and safety of different anticoagulation (AC) strategies for prevention of thromboembolic events, major bleeding, and all-cause mortality in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF). In this systematic review, we conducted a literature search to examine the possible association between different AC strategies and prevention of these adverse outcomes. Scientific databases (PubMed, EMBASE, and Scopus) were searched using relevant medical subject headings and keywords to retrieve studies published through September of 2019. Studies assessing the outcomes of interest in patients with HCM and AF receiving AC, no AC as well as direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) were selected. This review identified 14 observational studies evaluating thromboembolic events by AC strategies in 8,479 participants with concomitant HCM and AF. The use of AC was associated with a lower pooled incidence rate of total thromboembolic events at 9.5% (112 events in 1,175 patients) compared to 22.1% with no AC (108 events in 489 patients). In addition, the use of DOACs was associated with a lower pooled incidence rate of thromboembolic events at 4.7% (169 events in 3,576 patients) compared to 8.7% with VKAs (281 events in 3,239 patients). Furthermore, the use of DOACs compared to VKAs was associated with a lower pooled incidence rate of major bleeding and all-cause mortality at 3.8% (136 events in 3,576 patients) versus 6.8% (220 events in 3,239 patients) and 4.1% (124 events in 3,008 patients) versus 16.1% (384 events in 2,380 patients), respectively. AC of patients with concomitant HCM and AF was associated with a lower incidence of thromboembolic events when compared to antiplatelet therapy or no treatment. Treatment with DOACs was also associated with a lower incidence of thromboembolic events, major bleeding, and all-cause mortality when compared to VKAs.

Clinical Benefit of Direct Oral Anticoagulants Versus Vitamin K Antagonists in Patients with Atrial Fibrillation and Bioprosthetic Heart Valves

PurposeThe use of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and bioprosthetic heart valve is still controversial. The aim of this study was to compare the tolerability and effectiveness of treatment with DOACs versus vitamin K antagonists (VKAs) in patients with AF and a bioprosthetic heart valve in clinical practice. MethodsData for this study were sourced from the multicenter, prospectively maintained AF Research Database (NCT03760874), which includes all patients with AF undergoing follow-up at participating centers through outpatient visits every 3–6 months. The rates of occurrence of thromboembolic events (ischemic stroke, transient ischemic attack, systemic embolism), major bleed, and intracranial hemorrhage (ICH) were assessed. These data were used for quantifying the net clinical benefit (NCB) of DOACs versus VKAs, in accordance with the following formula: (Thromboembolic events incidence rate with VKAs – Thromboembolic events incidence rate with DOACs) – Weighting factor × (ICH rate with DOACs – ICH incidence rate with VKAs). The database was retrospectively queried for patients with AF who were prescribed a DOAC or VKA and had a history of bioprosthetic heart valve replacement. FindingsA total of 434 patients with AF (DOACs, n = 211; VKAs, n = 223) were identified. Propensity score matching identified 130 patients prescribed DOACs (apixaban, 55.4%; rivaroxaban, 30.0%; dabigatran, 13.1%; edoxaban, 1.4%) and the same number of VKA recipients (warfarin, 89.2%; acenocoumarol, 10.8%). The mean (SD) duration of follow-up was 26.8 (2.3) months. The incidence rates of thromboembolic events were 1.3 per 100 person-years in the DOAC group versus 2.0 per 100 person-years in the VKA group (P = 0.14). The incidence rates of major bleed events were 2.6 per 100 person-years in the DOAC group versus 4.9 per 100 person-years in the VKA group (P = 0.47). The incidence rates of ICH were 0.38 per 100 person-years in the DOAC group versus 1.16 in the VKA group (hazard ratio = 0.33; 95% CI, 0.05–2.34; P = 0.3). A positive NCB of DOACs over VKAs of +1.87 was found. ImplicationsAccording to these data from clinical practice, DOACs seem to be associated with a greater NCB versus VKAs in patients with AF with a bioprosthetic heart valve, primarily due to lower rates of both major bleeds and thromboembolic events.

PB2211 RESULTS FROM A REAL‐WORLD, RETROSPECTIVE STUDY EVALUATING THE THROMBOEMBOLIC EVENTS AND THE ASSOCIATED RISK FACTORS IN JAPANESE PATIENTS WITH POLYCYTHEMIA VERA

Background:Polycythemia vera (PV) is marked by hyperproliferation of erythroid, myeloid, megakaryocytic components in the bone marrow (clinically manifested as erythrocytosis, leukocytosis, and thrombocytosis) often resulting in thromboembolic events (TEs), cardiovascular complications (CVCs), and poorer prognosis for survival. The treatment of patients (pts) with PV is directed towards maintaining a strict hematocrit of &lt;45% to reduce the risk of TEs and CVCs. Age ≥60 years and history of thrombosis have mainly been associated with the emergence of TEs; additional risk factors like CVCs, leukocytosis, and presence of JAK2 mutation may further enhance the risk of TEs. Only few real‐world studies evaluated the occurrence of TEs in pts with PV in Japan. Here, we report the results from a retrospective study analyzing TEs and the associated risk factors in Japanese pts with PV.Aims:To evaluate the incidence of TEs, time to TEs, correlation of risk factors with TEs, and healthcare resource use in Japanese pts with PV.Methods:This was a retrospective study of pts with PV diagnosed per International Classification of Diseases (ICD‐10‐CM [C900] codes) during the study period from April 1, 2008 to August 31, 2015 in Japan. The health insurance claims data provided by Medical Data Vision (MDV Co., Ltd., Japan) were utilized for this study. The primary objective was to identify the number of pts with PV who had arterial/venous TE after PV diagnosis (overall incidence rate of TEs). The key secondary objectives included time to TEs, correlation of risk factors with TEs, healthcare resource use, and demographic/baseline pt characteristics. Leukocytosis and JAK mutation were not evaluated as risk factors (owing to study limitation [claims database analysis]).Results:Overall, 606 pts with PV were identified. The demographic and baseline pt characteristics of interest were as follows: male/female = 56.9%/43.1%; age (years): median (range) = 67.0 (23‐97; [&lt;60 = 25.7%, ≥60 = 74.3%]); time since PV diagnosis (months), median (range) = 21.770 (0.03‐86.26); risk factors: previous TEs = 11.6% pts, CVCs = 45.7% pts, ≥3 risk factors = 19.0% pts, age ≥60 years and previous TE = 9.9% pts, age ≥60 years or previous TE = 75.9% pts. In total, 200 events were observed in 147 pts (24.3%) at a rate of 13.81/100 person‐years (TE = 16.5%; death = 4.3%; nonhematologic malignancies = 3.3%; bleeding = 3.1%; and disease progression [myelofibrosis/acute myeloid leukemia] = 2.1%). Overall, 100 pts (16.5%) had a TE (118 events) at a rate of 8.15/100 person‐years. The most commonly reported TE was ischemic stroke (10.7%), followed by venous thromboembolism (2.8%), acute myocardial infarction (2.3%), transient cerebral ischemic attack (1.2%), and peripheral arterial thrombosis (0.5%). The correlation between TEs and risk factors (age, history of thrombosis, CVCs, and number of risk factors) are presented in Table (A). The thromboembolic event‐free survival rate was 69.3% (time to TE, Figure [B]). The annual total healthcare costs (mean [per person]) were significantly impacted by the presence of TEs (yes [n = 100] vs no [n = 506]: ¥992536.2 vs ¥459137.6; P&lt;0.001).Summary/Conclusion:As reported by other population‐based analyses, results from this real‐world MDV database analysis confirm that age ≥60 years, history of thrombosis, CVCs, and presence of ≥3 risk factors increase the risk of TE occurrence (univariate analysis). This highlights the need for risk‐adaptive therapy for these pts with PV in Japan. The study results are based on hospital‐based claims; hence, warrant careful interpretation and further confirmation in clinical trial/real‐world setting.image

Bevacizumab combined with platinum\u2013taxane chemotherapy as first-line treatment for advanced ovarian cancer: a prospective observational study of safety and efficacy in Japanese patients (JGOG3022 trial)

BackgroundThis was the first large-scale prospective observational Japanese study evaluating the safety and efficacy of bevacizumab combined with paclitaxel and carboplatin for newly diagnosed advanced ovarian cancer.MethodsPatients were prospectively enrolled in the primary analysis cohort if they had Stage III or IV epithelial ovarian/fallopian tube/primary peritoneal cancer and were scheduled to receive paclitaxel plus carboplatin every 3 weeks in Cycles 1–6 and bevacizumab every 3 weeks in Cycles 2–22. Primary endpoints were bevacizumab-specific adverse events and adverse events ≥ Grade 3. Secondary endpoints were progression-free survival (PFS) and the response rate.ResultsAmong 346 patients enrolled, 293 patients formed the primary analysis cohort. Regarding bevacizumab-specific adverse events ≥ grade 3, incidence rates of thromboembolic events (1.4%), gastrointestinal perforation (0.3%), fistula (0.7%), wound dehiscence (0%), and bleeding (0%) were very low. While incidence rates of hypertension (23.2%) and proteinuria (12.6%) were high, all such events were tolerable. No patient with prior bowel resection developed perforation or fistula. Median PFS was 16.3 months (95% CI 14.5–18.9). The response rate was 77.5% (95% CI 67.4–85.7). The response rate was 63.6% in patients with clear cell carcinoma, which tended to be better than previously reported. The median platinum-free interval was 11.5 months, and the platinum-resistant recurrence rate was 24.5%.ConclusionsCombining bevacizumab with chemotherapy was tolerable and efficacy was acceptable in Japanese patients with advanced epithelial ovarian cancer. Bevacizumab seems to reduce platinum-resistant recurrence and is promising for clear cell carcinoma.